Event-free survival and complete response rate as surrogate endpoints for overall survival in high-risk non-muscle-invasive bladder cancer: a meta-analysis of Bacillus Calmette-Guérin–naïve or –remote cases
Cancer, 2025
In oncology trials, overall survival (OS) is traditionally regarded as the gold standard endpoint for assessing the effectiveness of an investigational therapy. However, in early-stage cancers such as high-risk non-muscle-invasive bladder cancer (HR NMIBC), the long follow-up times typically required for the generation of OS data can delay regulatory and reimbursement decisions. Guidelines from the International Bladder Cancer Group and the Society for Immunotherapy of Cancer have recommended intermediate endpoints such as event-free survival (EFS) and complete response rate (CRR) to facilitate drug development and accelerate patient access to effective therapies. However, their surrogacy relationship with OS (i.e., their ability to predict treatment effects on OS) has not been validated.
To help address this, an Analysis Group team led by Vice Presidents Kalé Kponee-Shovein and Yan Song and Associates Yipeng Gao and Jingyi Liu collaborated with researchers from Merck and The University of Texas MD Anderson Cancer Center on a first-of-its-kind study that systematically assessed the surrogacy relationship between both EFS and OS and CRR and OS among patients with HR NMIBC. The researchers conducted a systematic literature review and meta-analysis of aggregate data from published clinical trials conducted in patients with BCG-naïve or remote HR NMIBC.
In an article on their research, the authors detail their findings, including evidence supporting EFS as a surrogate endpoint for OS among the patients studied. They conclude that their findings reinforce the potential of EFS to reliably predict treatment effects on OS among BCG-naïve or BCG-remote patients with HR NMIBC. They also found an association between OS and CRR, noting that further evidence from larger clinical trials will be critical going forward to help understand CRR’s role.
Authors
Bhattacharya R, Kponee-Shovein K, Gao Y, Song Y, Liu J, Wei K, Kapadia E, Li H, Kama AM